Purpose:

The objective of this study was to systematically review the evidence for the efficacy of pharmacologic and nonpharmacologic treatments in alleviating dyspnea in patients with terminal cancer.

Literature Evaluated:

Literature evaluated included 37 studies, plus one abstract initially reviewed. A final set of 18 studies was included; 7 assessed opioids, 6 assessed oxygen- or helium-enriched air, 1 assessed furosemide, and 4 assessed nonpharmacologic interventions. Meta-analysis was not completed due to the paucity of studies and heterogeneous outcome measures.

Sample Characteristics :

Sample Size Across Studies:

Opioid intervention = 256 patients

Oxygen or helium = 148 patients

Furosemide intervention = 7 patients

Nonpharmacologic intervention = 403 patients

Sample Range Across Studies:

Opioids = 9–101 patients

Oxygen or helium = 12–51 patients

Nonpharmacologic = 34–203 patients

With respect to gender, age, and diagnosis within the sample, the opioids subgroup included both genders. The median age range was 56–73 years. The majority had primary lung cancer, and both opioid-tolerant and opioid-naïve participants were included.

The oxygen or helium subgroup included both genders. The median age range was 64–72 years. The majority had primary lung cancer.

No comment was available on gender or age for the nonpharmacologic subgroup, but the primary diagnosis was lung cancer.

Results:

The primary outcome was subjective dyspnea relief according to the visual analog scale (VAS) or dyspnea intensity according to the modified Borg scale. The secondary outcome was oxygen saturation and adverse effects.

Opioid Intervention:

The administration of subcutaneous morphine resulted in significant reduction in dyspnea according to the VAS compared with placebo.

Nebulized morphine versus placebo failed to demonstrate a significant effect of nebulized morphine. No difference in dyspnea VAS score was observed in one trial when nebulized morphine was compared with subcutaneous morphine, although patients preferred the nebulized route.

In one trial, the addition of benzodiazepines (midazolam) to morphine was significantly more effective than morphine alone, without additional adverse effects.

Oxygen Intervention:

Oxygen was not superior to medical air for alleviating dyspnea, except for patients with hypoxemia.

Furosemide Intervention:

One small trial assessed the use of nebulized furosemide with a trend toward worsening dyspnea.

The nurse-led breathlessness rehabilitation techniques and education and advice regarding coping with the psychological aspects of the symptoms assessed the primary outcome of dyspnea relief after weeks.

All nurse-led interventions proved to be beneficial, improving breathlessness and quality of life in terms of physical, psychological, and emotional aspects.

Conclusions:

No evidence supports subcutaneous morphine as effective in treating dyspnea in patients with advanced cancer.

Use of oxygen to alleviate dyspnea in nonhypoxic patients with cancer cannot be recommended. Supplemental oxygen is expensive and can restrict mobility with possible decrease in quality of life. Use of medical air (78.9% nitrogen, 21.1% oxygen) was shown to be effective in reducing the sensation of dyspnea. However, this intervention is not used routinely in care settings.

This review recommended integration of pharmacologic and nonpharmacologic interventions, such as those used in nurse-led programs to relieve dyspnea.

Limitations:

Acknowledging the paucity of evidence from randomized controlled trials to support the interventions is important.

Limitations of this review were

Few randomized controlled trials

Small studies

Short follow-up in opioid studies

Lack of consistency regarding opioid doses.

Nursing Implications:

A major research opportunity exists to further document outcomes from nurse-led dyspnea interventions.